An efficient oxidative conversion of 2-aryl-2H-chromenes to the corresponding flavones by tert-butylhydroperoxide and copper bromide

Article abstract of DOI:10.1016/j.tetlet.2016.03.006

A simple and efficient method has been developed for the facile oxidation of chromenes to the corresponding flavones by tert-butylhydroperoxide (TBHP) in the presence of copper(II) bromide catalyst in toluene at 80 °C in a very short time. The reaction demonstrates excellent reactivity, functional group tolerance, and good to excellent yields without using conventional strong oxidizing agents.

Full text of DOI:10.1016/j.tetlet.2016.03.006

Accepted Manuscript
An efficient oxidative conversion of 2-aryl-2H-chromenes to the corresponding
flavones by tert-butylhydroperoxide and copper bromide
Dipanwita Banerjee, Utpal Kayal, Gourhari Maiti
PII:
S0040-4039(16)30228-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.03.006
TETL 47394
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
4 December 2015
22 February 2016
2 March 2016
Please cite this article as: Banerjee, D., Kayal, U., Maiti, G., An efficient oxidative conversion of 2-aryl-2H-
chromenes to the corresponding flavones by tert-butylhydroperoxide and copper bromide, Tetrahedron Letters
(
2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.03.006
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Graphical Abstract
An efficient oxidative conversion of
Leave this area blank for abstract info.
2
-aryl-2H-chromenes to the
corresponding flavones by tert-
butylhydroperoxide and copper
bromide
Dipanwita Banerjee, Utpal Kayal and Gourhari Maiti
O
TBHP (2.0 equiv.)
O
R
R'
CuBr (10 mol %)
toluene, 80 C
O
R
2
R'
0

1
Tetrahedron Letters
An efficient oxidative conversion of 2-aryl-2H-chromenes to the corresponding
flavones by tert-butylhydroperoxide and copper bromide
Dipanwita Banerjee, Utpal Kayal and Gourhari Maiti*
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and efficient method has been developed for the facile oxidation of chromenes to the
corresponding flavones by tert-butylhydroperoxide (TBHP) in presence of copper (II) bromide
0
catalyst in toluene at 80 C in a very short time. The reaction demonstrates excellent reactivity,
functional group tolerance and good to excellent yields without using conventional strong
oxidizing agents.
Available online
Keywords:
2
-aryl-2H-chromenes
2
009 Elsevier Ltd. All rights reserved.
flavones derivatives
tert-butylhydroperoxide (TBHP)
copper (II) bromide
oxidative conversion
very short reaction time
Flavones are natural products of the benzopyran class,
constituting an important member of oxygen heterocycles that are
widely distributed in the vascular plant kingdom and dietary
Strong oxidizing agents and/or harsh reaction condition such as
6a 6d 6f
2
CrCl , KMnO
4
2
KO in DMSO etc.
1
In continuation to our effort towards the synthesis and reaction
components as secondary metabolites. Their low toxicity and
11
12
2
of flavones and chromenes herein, we wish to disclose an
efficient method for the late stage oxidation of chromenes to
flavones, by using tert-butyl hydroperoxide (TBHP) in presence
of non precious metal salt, Cu(II)bromide (Scheme 1) catalyst.
extensive biological and pharmaceutical activities, including
2
o,2p
2q
2r,2s
antioxidant,
antitumor
anti-inflammatory,
antibacterial
and
2
t,2u
have led them to the development of a variety of
general approaches for synthesizing their large number of
3
derivatives or analogs. The main synthetic effort towards the
synthesis of flavones are divided into four major classes
depending on the starting compounds. Cyclodehydration of 1-(2-
4
hydroxyphenyl)-3-arylpropane-1,3-dione, cyclization of o-
5
6
alkynoylphenols, oxidation of chromenes and coupling reaction
7
of substituted phenols are four major approaches to afford
flavone and its derivatives. In addition to these there are several
recent reports of solid state reaction such as microwave
Scheme 1: Oxidative conversion of chromene to flavone
8
irradiation and high- speed ball milling (HSBM) for the
We began this study with 2-phenyl-2H-chromene as a model
substrate and TBHP as a stoichiometric oxidant. For our initial
studies, we used 1-2 equivalent of TBHP with respect to
chromene and evaluated the metal salts, reaction temperature and
also reaction protocol.
9
synthesis of flavonoid and neoflavonoid. However, many of the
reported methods often suffer from the drawback of harsh
reaction conditions, tedious work up procedures, long reaction
time and or low to moderate yields, especially, in case of
cyclization of o-alkynoylphenols, where 5-exo-dig cyclization
10
At first a variety of metal salts as catalysts were examined in
presence of TBHP (1 to 2 equiv.) in refluxing acetonitrile solvent
and results are summarized in Table 1. From Table 1 it is found
that amongst the various copper and other metal salts catalyst, the
proceeds competitively against a desired 6-endo-dig mode that
leads to aurones. Despite the several synthetic methods were
known to construct flavones and their derivatives, the
development of more general and highly efficient methods is still
an active area of research.
2
CuBr was found to exhibit the best catalytic activity. It may be
mentioned here that the reaction proceeds in absence of TBHP
(entry 15, table 1) but the yield is very low. When the same
reaction was carried out using 2 equivalent of TBHP only
There are only a few methods are known in the literature for
the oxidative conversion of chomenes to flavones using very
_
__________________________
without the use of CuBr
yield (46%, entry 14, table 1) and also the longer reaction time is
required. By using a combination of CuBr and two equivalent of
2
, the reaction proceeds but with lower
*
Corresponding author: E-mail address: ghmaiti123@yahoo.co.in
2
Tel. No.: +91 33 2414 6223; Fax No.: +91 33 2414 6223
TBHP in refluxing acetonitrile solvent gave 76 % yield (entry 3,
Table 1) of the desired product.

2
a,b
Table 1: Optimisation of catalyst
reaction condition. The results are summarized in Table 2. By
performing the same reaction under open air (entry 10, table 2)
condition and we did not find any significant difference in terms
of yield and reaction time in comparison to the argon atmosphere
reaction condition. Hence there is no role of oxygen in this
transformation. From this study we can conclude that both TBHP
and CuBr
Thus, 10 mol % CuBr
in decane) in toluene solvent at 80 C was found to be the best
2
might play an important role in this transformation.
2
in presence of 2 equivalent of TBHP
0
(
13
possible reaction condition in term of yields and reaction time.
To evaluate the generality of this reaction, using an optimized
reaction protocol, we performed the oxidation of various
chromenes and the results are summarized in Table 3. Different
functional groups including electron-donating and electron-
withdrawing groups in various positions in both phenyl rings
were exhibited good level of tolerance under the reaction
condition.
a,b
Table 3. Oxidative conversion of chromenes to flavones
a
Reaction conditions: Chromene (1.0 mmol), tert butylhydroperoxide
(
2.0 mmol) acetonitrile (2 mL), under argon atmosphere, 2-8h.
Yields refer to pure and isolated product.
b
a
Table 2: Optimization of reaction condition and solvents
Entry
Solvents
Diethyl ether
DCM
Temp (°C)
Time
Yield (%)
1
2
35
5 h
10
35
40
56
66
80
80
5 h
5 h
5 h
5 h
3
4
5
6
Acetone
8
THF
59
56
76
Ethanol
Acetonitrile
5 h
iPrOH
7
8
9
80
80
80
80
5 h
5 h
58
63
1,4-Dioxane
Toluene
5 min
5 min
5 h
94
1
0b
Toluene
92
1
1
2
DMF
80
80
24
5
1
-
5 h
a
Reaction
conditions:
Chromene
(1.0
mmol),
tert
butylhydroperoxide, under argon atmosphere, CuBr
solvent (2 mL). Results in open air condition
2
(10 mol %),
b
To improve the yield of the desired product further, the reaction
is optimized by varying the reaction temperature using various
solvents. A series of solvents such as diethyl ether, DCM,
acetone, THF, ethanol, isopropanol, toluene, 1,4-dioxane, DMF
etc and also the reaction temperature were tested to optimized the

3
and also from the above results. At first the low valent Cu(II)
salt donates an electron to TBHP and is oxidized to Cu(III)-OH
species producing the tert-butyloxy radical, which then abstract a
hydrogen atom from the benzylic position of the substrate and
generate a new benzylic radical. The resulting radical then
combine with tert butylperoxy radical produced by reduction of
Cu(III)-OH salt, followed by oxidative decomposition afforded
the desired product.
In conclusion, we have demonstrated that the oxidative
conversion of various chromenes to the corresponding flavone
derivatives under simple reaction condition with excellent yields.
Compared to the reported methods, this method has the
advantages of very short reaction time, avoiding the use of toxic
transition metal, wide applicability and convenient manipulation.
Acknowledgements
Financial support and instrumental facilities from the DST-
PURSE, FIST and UGC-CAS programs, New Delhi to the
Department of Chemistry, Jadavpur University is gratefully
acknowledged. DB and UK thank CSIR, New Delhi for award of
their fellowships.
Supplementary Material
Supplementary data associated with this letter can be found, in
the online version, at
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1
2
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crystalline solid, mp 95–96 °C (lit. 96–97 °C); H NMR (300
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5
Highlights
A simple and an efficient oxidative conversion of chromenes to flavones.
A very short reaction time and high level of functional group tolerance.
Non precious metal salt, Cu(II) bromide is used as a catalyst.
Wide applicability (21 examples) and good to excellent yields (67-94%).